Preparation and pyrolysis of 1-(pyrazol-5-yl)-1,2,3-triazoles and related compounds

Article abstract of DOI:10.1039/a700421d

1-(Pyrazol-5-yl)-1,2,3-triazoles 8a, 9a and 10 are prepared by cycloaddition of 5-azidopyrazoles with methyl prop-2-ynoate. The regiochemistry of the process is confirmed by synthesis of 9a using an authentic route from ethyl 2-formyl-2-diazoacetate 13. Flash vacuum pyrolysis of 8a, 9a and 10 gives 5-methoxypyrazolo[1,5-a]pyrimidin-7-ones 16-18 by a mechanism involving an unexpected oxoketenimineimidoyl ketene rearrangement as the key step. The mechanism is supported by a ¹³C labelling experiment. A general route to pyrazolo[1,5-a]pyrimidin-7-ones from pyrazolylaminomethylene Meldrum's acid derivatives (e.g. 30-32) is also reported.

Full text of DOI:10.1039/a700421d

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Preparation and pyrolysis of 1-(pyrazol-5-yl)-1,2,3-triazoles and
related compounds1
David Clarke,a Richard W. Maresb and Hamish McNab*,b
a
Kodak European Research and Development, Headstone Drive, Harrow, Middlesex,
UK HA1 4TY
b Department of Chemistry, The University of Edinburgh, West Mains Road, Edinburgh,
UK EH9 3JJ
1-(Pyrazol-5-yl)-1,2,3-triazoles 8a, 9a and 10 are prepared by cycloaddition of 5-azidopyrazoles with
methyl prop-2-ynoate. The regiochemistry of the process is confirmed by synthesis of 9a using an
authentic route from ethyl 2-formyl-2-diazoacetate 13. Flash vacuum pyrolysis of 8a, 9a and 10 gives 5-
methoxypyrazolo[1,5-a]pyrimidin-7-ones 16–18 by a mechanism involving an unexpected oxoketenimine–
imidoyl ketene rearrangement as the key step. The mechanism is supported by a 13C labelling experiment.
A general route to pyrazolo[1,5-a]pyrimidin-7-ones from pyrazolylaminomethylene M eldrum’s acid
derivatives (e.g. 30–32) is also reported.
The formation of indoles by photolysis or pyrolysis of 1-aryl-
1,2,3-triazoles is well known 2,3 (Scheme 1), and the present
derivative 6 decomposed under these conditions, cycloaddition
with 7 was successfully accomplished in boiling acetonitrile
solution (81ЊC) and only a single isomer 10 precipitated in 45%
yield. After purification, the triazoles 8–10 were obtained with
water (or solvent) of crystallisation.
Dimethyl acetylenedicarboxylate reacted with 5-azido-3-
phenylpyrazole 6 in refluxing acetonitrile to give the triazole
11 (30%), but other dipolarophiles such as ethyl phenylprop-2-
ynoate, phenylacetylene, phenyl vinyl sulfoxide and ethyl
trimethylsilylprop-2-ynoate were of insufficient reactivity to
compete with azide decomposition (see Experimental section).
Similarly, 2-azidoimidazole 12 did not react cleanly with methyl
prop-2-ynoate 7 in refluxing toluene.
N
N
N
N
H
N
H
Scheme 1
study was initiated in an attempt to extend the methodology to
the preparation of fused heterobicyclic five-membered ring sys-
tems including imidazopyrazoles. In the event, an unexpected
rearrangement took place1 leading to pyrazolopyrimidinone
systems via an oxoketenimine–imidoyl ketene interconversion.
We now present full details of this work, certain aspects of
which have been reinvestigated recently by Fulloon and
Wentrup.4
CO2Me
MeO2C
N
N
H
N3
H
N
N
Ph
N
N
N
5-Aminopyrazoles 1–3 are readily available, and can be easily
transformed to the corresponding azido derivatives 4–6 in 46–
99% yield by diazotisation and treatment with sodium azide.5
We therefore investigated the cycloaddition of these azides with
electron-deficient alkynes as the initial route to the key 1-
(pyrazol-5-yl)triazole precursors (Scheme 2). It was necessary
11
12
CO2Me
N
MeO2C
N
N
H
N
H
N
N
R
R
N
N
N
N
CO2Me
N
NH2
H
N3
H
N
H
8a R = H
9a R = But
10 R = Ph
8b R = H
9b R = But
N
i
ii
R
R
R
O
N
N
N
N
N
N
OMe
It is known that cycloaddition of arylazides with electron-
deficient alkynes generally favours the configuration found in
the adducts 8a and 9a, although often the regioselectivity is
low.6,7 The major adducts 8–10 are clearly related structurally,
since the triazole protons show similar high frequency chemical
shifts (δH 9.18–10.17); the corresponding resonances of the
minor isomers (where present) occur at much lower frequency
(e.g. 8b δH 8.44). An attempted NOE experiment to prove the
regiochemistry was unsuccessful and so it was necessary to
develop an unambiguous synthetic route. A possible route was
reported almost 30 years ago by Stojanovic and Arnold,8 who
showed that ethyl 2-formyl-2-diazoacetate 13, which can be
7
1 R = H
4 R = H
5 R = But
6 R = Ph
8 R = H
9 R = But
10 R = Ph
2 R = But
3 R = Ph
Scheme 2 Reagents and conditions: i, NaNO2, HCl, then NaN3; ii, heat
to select conditions which were sufficiently mild to avoid the
thermal degradation of the azide. Thus cycloaddition of the
azides 4 and 5 with methyl prop-2-ynoate 7 occurred smoothly
in refluxing toluene (110 ЊC) and the triazoles 8 (86%) and 9
(79%), respectively, precipitated from solution as ca. 5:1 mix-
tures of regioisomers (see below). Although the 3-phenyl
J. Chem. Soc., Perkin Trans. 1, 1997
1799

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made in two steps from N,N-dimethylformamide, reacts with
aniline derivatives to give ethyl 1-aryl-1,2,3-triazole-4-
carboxylates in good yield (Scheme 3). Thus when 13 was
parent system 8a still showed two sets of doublets (3J 1.8 Hz)
which confirmed that any cyclisation could not have taken place
onto the 4-position of the pyrazole. The remaining proton
(derived from the triazole ring) resonated at δH 5.26. However,
the IR spectra of the pyrolysis products surprisingly showed no
ester carbonyl stretch in the range 1715–1800 cmϪ1. In addition,
the chemical shift of the proton at the 2-position of authentic
6-methylimidazo[1,2-b]pyrazole9 is δH 6.95; it is inconceivable
that an adjacent ester substituent could cause a low frequency
shift of nearly 1.7 ppm, and so the imidazo[1,2-b]pyrazole
system 15 was ruled out as the product from the pyrolyses.
An NOE experiment on the product of the pyrolysis of the
phenyl derivative 10 showed enhancement of the methoxy sig-
nal (4%) on irradiation of the peak at δH 5.31 and vice versa
(8%); these effects are also much larger than would be expected
if the methoxy group had been part of an ester substituent, and
imply that the methoxy group is close in space to the proton at
δH 5.31. Irradiation of the ortho protons of the phenyl group
showed only the expected enhancements of the meta protons
(12%) and the adjacent proton derived from the pyrazole ring
(18%), and so the connectivity of this portion of the molecule
has not been affected by the pyrolysis.
CO2Et
CO2Et
H
H
i
ii
iii
H
+
•
N+
•
•
N
Me2N
O
Me2N
Cl
N
N–
O
Cl–
N
Ar
13
•
=
13C (for synthesis of 9a*)
Scheme 3 Reagents and conditions: i, (COCl)2; ii, EtO2CCHN2; iii,
ArNH2
reacted overnight with 5-amino-3-tert-butylpyrazole 2 in etha-
nol containing some acetic acid, the triazole 14 was obtained in
81% yield. This compound showed the triazole proton reson-
ance at δH 10.12, which clearly shows that the major product of
the cycloaddition is the adduct 9a as expected. This was further
confirmed by an ester exchange reaction of 14 in methanol con-
taining sodium methoxide to give a compound in 98% yield
which was identical with 9a.
The 5-methoxypyrazolo[1,5-a]pyrimidin-7-one structures
16–18 are consistent with these observations (Scheme 4, route
b); in particular the position of the electron-donating methoxy
substituent adjacent to the isolated proton (6-position) explains
the results of the NOE experiments and the low frequency res-
onance of this proton. The formation of this structure requires
that a skeletal rearrangement of the non-pyrazolic portion of
the molecule has occurred. This was confirmed by synthesis and
pyrolysis (600 ЊC, 10Ϫ3 Torr) of ethyl 1-phenyl-1,2,3-triazole-4-
carboxylate8 19 (Scheme 5), which gave the quinolone 21, iden-
CO2Et
N
N
N
But
N
N
H
14
The pyrazole ring protons show similar chemical shifts for
both regioisomers. In addition, there is an indication from the
magnitude of JH H in the pyrazole rings of 8a and 8b (ca. 1.9
CO2R
3
H
H
Hz) that both isomers may exist in solution as the 1H-tautomer
shown, possibly due to intramolecular hydrogen bonding with
the 2-nitrogen atom of the triazole ring.
N
O
N
OR
R = Et
N
N
N
The 1,2,3-triazoles 8a, 9a and 10a were pyrolysed under FVP
conditions at 600 ЊC (10Ϫ2–10Ϫ3 Torr) and clean single products
condensed in each case at the exit point of the furnace. The
mass spectra of these materials showed the correct molecular
ion expected for loss of dinitrogen from the triazoles, followed
by the expected cyclisation to the imidazo[1,2-b]pyrazole sys-
tem 15 (Scheme 4, route a). The product from pyrolysis of the
O
O
19 R = Et
20 R = Me
22 R = Me
H
H
N
N
OH
O
CO2Me
O
O
N
N
21
N
Scheme 5
R
N
N
tical in all respects with a commercially available authentic
sample. The dealkylation of the ethoxy group may occur as a
subsequent thermal process by a cis-elimination mechanism
(Scheme 5), which is well known for 2-alkoxypyridines and
related compounds.10 However, the corresponding methyl ester
20 has been recently pyrolysed by Fulloon and Wentrup,4 and
the expected methoxyquinolone 22 was isolated as the major
product, particularly at high temperatures.
H
i
CO2Me
N
R
N
N
H
To account for the formation of 16–18 the mechanism shown
in Scheme 6 was proposed.1 An equivalent scheme can account
for the formation of the quinolone 22. The first step involves
the well precedented 2,3 formation of the imidoyl carbene 23,
followed by its insertion into the adjacent C–H bond to gener-
ate the ketenimine carboxylic ester 24. Such insertions are well
known in general in gas-phase carbene chemistry11 and the 1,2-
shift in imidoyl carbenes in particular is also known.12 In an
attempt to circumvent this step of the mechanism, the 5-
substituted triazole 11 was pyrolysed, but although extrusion of
nitrogen was noted by the rise in pressure in the vacuum line, no
useful products were isolated.
b
a
X
H
N
H
OMe
N
R
R
N
N
N
N
CO2Me
O
16 R = H
17 R = But
18 R = Ph
15
Scheme 4 Reagents and conditions: i, FVP, 600 ЊC, 0.001 Torr
1800
J. Chem. Soc., Perkin Trans. 1, 1997

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CO2Me
N
CO2Me
N
atoms in 6-membered ring enone systems may be expected to be
insignificant.14 The remaining resonance at δC 160.80 was there-
fore assigned as due to the 5-position; in agreement with this
interpretation, the corresponding signal of the known quin-
olone 22 (R᎐Me) appears at δ 160.5.15
•
•
N
N
N
N
R
R
N
N
᎐
C
N
N
When the 13C labelled precursor 9* was pyrolysed under
identical conditions to those of its unlabelled analogue, the only
enhanced signal in the 13C NMR spectrum of the pyrolysate
was that due to the quaternary C-5 (δC 160.92) of 17*, in
agreement with the mechanism of Scheme 6. In the particular
pyrolysis, a minor peak was also observed at δC 165.01 which is
due to an unidentified impurity. This is unlikely to be the
imidazo[1,2-b]pyrazole 29*, since the C-2 resonance in this
system generally occurs at δC < 120.16
H
8–10
H
CO2Me
H
H
•
N
N
•
O
R
R
N
N
MeO
N
N
H
H
The final step of the mechanism (Scheme 6) involves
regiospecific cyclisation of the ketene intermediate 25 to the
final product. An alternative route to this energy surface was
developed by pyrolysis of the Meldrum’s acid derivatives 30–32
which were obtained from the appropriate aminopyrazoles and
either methoxymethylene Meldrum’s acid 33 or the ketene thio-
acetal 34 by standard methods (see Experimental section). FVP
of 30–32 at 600 ЊC generated methylene ketene intermediates
which isomerise by 1,3-H shift to the imidoyl ketenes. As
expected, these cyclise to the pyrazolo[1,5-a]pyrimidin-7-ones
35–37 in ca. 50% yield with no trace of isomeric products
(Scheme 7). Examples of this ring system have been investigated
24
23
N
OMe
H
N
O
OMe
H
•
•
R
R
16–18
N
N
N
N
•
H
H
O
25
•
=
13C for 9a*
Scheme 6
The key step of the rearrangement is the methoxy migration
in the ketenimine 24 to give the imidoyl ketene 25. Facile 1,3-
shifts of thioalkoxy groups on this energy surface have been re-
ported 13 and, subsequent to our preliminary communication,1
Fulloon and Wentrup have identified both the ketenimine
26 and the imidoyl ketene 27 (related to 24 and 25, respectively)
en route to the quinolone 28 by matrix isolation.4 This step of
the mechanism is therefore secure.
O
O
O
N
R′
•
•
H
O
O
H
N
H
N
•
R′
N
R′
O
N
N
N
H
R
N
N
H
H
R
H
N
OMe
H
R
N
•
O
30 R = R′ = H
31 R = Me, R′ = H
32 R = But, R′ = MeS
•
MeO
O
H
N
26
27
R′
H
N
H
R
N
OMe
N
N
But
•
O
N
N
35 R = R′ = H
36 R = Me, R′ = H
37 R = But, R′ = MeS
CO2Me
O
28
29*
Scheme 7
The overall effect of the 1,2-H shift and the 1,3-MeO shift is
that the original triazole methine carbon atom (C-5) becomes
the quaternary carbon (also C-5) in the product, and we sought
to prove this by a 13C labelling experiment involving the pre-
cursor 9a *. This was made by reaction of the aminopyrazole
2 with labelled formyldiazoacetate ester (Scheme 3, labelled
atoms highlighted) which was itself derived from dimethyl-
[13C]formamide. Before the pyrolysis, it was first necessary to
assign unambiguously the quaternary carbon atoms in a prod-
uct, and the phenyl derivative 18 was chosen for detailed study.
The five signals in question occur at δC 160.80, 157.20, 152.72,
as anti-inflammatory agents,17 and the present route provides
a convenient alternative synthesis.
O
O
O
O
O
O
O
O
OMe
MeS
SMe
33
34
1
140.41 and 132.67; the last appeared as a triplet in the H-
coupled spectrum, and is due to the ipso carbon atom of the
phenyl group. Similarly, the bridgehead carbon atom (C-3a)
would be expected to occur as a doublet due to coupling to H-3,
and this was observed at δC 140.41. The corresponding position
of the signal at δC 152.72 in compounds 16 and 17 was highly
substituent dependent, and is therefore due to C-2. The peak at
δC 157.20 appeared as a singlet in the 1H-coupled spectrum and
As an extension of this part of the work, the aminotriazole
derivative 38 was also pyrolysed, and two isomeric triazolopy-
rimidinones 39 and 40 which could not be separated by chroma-
tography were obtained in 76% overall yield. Surprisingly, the
proportion of these products was temperature dependent, with
one component (36% of the mixture at 400 ЊC) rising to 69% at
700 ЊC, with a corresponding change in the percentage of the
other component. Identification of the isomers was made by
2
was assigned as the carbonyl carbon atom, since JCH of such
J. Chem. Soc., Perkin Trans. 1, 1997
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Methyl 1-(1H-pyrazol-5-yl)-1H-1,2,3-triazole-4-carboxylate 8
A solution of 5-azidopyrazole 4 (1.42 g, 13 mmol) and methyl
prop-2-ynoate 7 (1.7 g, 1.8 cm3, 20 mmol) in toluene (7 cm3) was
heated to reflux under a nitrogen atmosphere for 2.5 h. On
cooling a brown precipitate was formed, which was found to be
a 4.6:1 mixture of two isomers (2.16 g, 86%, both isomers).
Crystallisation from acetic acid gave the major isomer methyl 1-
(1H-pyrazol-5-yl)-1H-1,2,3-triazole-4-carboxylate 8a, mp 254–
255 ЊC (from acetic acid) (Found: C, 43.4; H, 3.9; N, 35.3.
C7H7N5O2ؒ0.1 CH3CO2H requires C, 43.4; H, 3.6; N, 35.2%);
δH ([2H6]DMSO) 13.38 (1H, br s), 9.18 (1H, s), 7.99 (1H, m),
6.79 (1H, m) and 3.87 (3H, s); δC([2H6]DMSO) 160.37 (q),
145.12 (q), 138.92 (q), 131.40, 126.68, 97.06 and 51.89; m/z 193
(Mϩ, 17%), 164 (11), 162 (17), 135 (12), 134 (100), 133 (21), 107
(36) and 106 (42).
O
O
N
H
N
H
N
O
O
H
N
N
N
N
N
N
N
N
O
O
N
39
40
H
38
13C NMR spectroscopy, since it is know that the chemical shift
of the free ‘triazole’ ring carbon atom is dishielded by ca. 20
ppm in the [1,5-a] isomer 39 relative to the alternative [4,3-a]
isomer 40.18 The spectrum of the mixture obtained from a
700 ЊC pyrolysis showed two major and two minor CH peaks in
the range δC 133–153, due to the ‘triazole’ carbon atoms and the
carbon atoms adjacent to the NH of the six-membered ring.
These were distinguished by a fully-coupled 13C NMR spec-
trum of the mixture. Thus the ‘triazole’ CHs occurred as simple
doublets with large one-bond coupling constants at δC 151.93
The minor isomer methyl 1-(1H-pyrazol-5-yl)-1H-1,2,3-
triazole-5-carboxylate 8b was identified by NMR spectroscopy;
δH ([2H6]DMSO) 8.44 (1H, s), 7.96 (1H, unresolved from major
isomer), 6.64 (1H, m) and 3.78 (3H, s); δC([2H6]DMSO) 157.54
(q), 143.93 (q), 136.93, 130.43, 129.64 (q), 101.54 and 52.54.
Methyl 1-(3-tert-butyl-1H-pyrazol-5-yl)-1H-1,2,3-triazole-4-
carboxylate 9a
1
1
(major, J 209.0 Hz) and 133.23 (minor, J 222.8 Hz), whereas
the six-membered ring carbon atoms resonated as a doublet of
doublets at δC 140.60 (major, 1J 183.6, 2J 3.3 Hz) and as a broad
5-Azido-3-tert-butylpyrazole 5 (0.687 g, 4.16 mmol) and methyl
prop-2-ynoate 7 (0.70 g, 8.33 mmol) were dissolved in toluene
(5 cm3) and the reaction mixture was heated to reflux for 3 h
under a nitrogen atmosphere. The mixture was cooled and a
yellow precipitate was isolated. The crude product (79%) was
recrystallised from ethyl acetate to give methyl 1-(3-tert-butyl-
1H-pyrazol-5-yl)-1H-1,2,3-triazole-4-carboxylate 9a (0.72 g,
70%), mp 192–193 ЊC (from ethyl acetate) (Found: C, 53.0; H,
6.1; N, 28.1. C11H15N5O2 requires C, 53.0; H, 6.05; N, 28.1%);
δH 10.17 (1H, s), 6.65 (1H, s), 4.06 (3H, s) and 1.42 (9H, s) (NH
signal not apparent); δC 162.65 (q), 155.71 (q), 145.78 (q),
139.36 (q), 126.59, 92.87, 52.56, 31.28 (q) and 29.78; m/z 249
(Mϩ, 51%), 220 (40), 218 (18), 206 (100), 190 (94), 179 (32), 174
(70) and 150 (18).
1
doublet at δC 148.20 (minor, J 180.8 Hz) with rather smaller
coupling constants. The ‘triazole’ CHs are indeed separated by
ca. 20 ppm; the major (thermodynamic) product at 700 ЊC has
the more deshielded ‘triazole’ carbon atom and is therefore
identified as the [1,5-a] isomer 39. Hence the kinetic product
40 is formed by cyclisation onto the 4-position of the initial
‘triazole’.
Experimental
1H and 13C NMR spectra were recorded at 200 and 50 MHz
respectively for solutions in [2H]chloroform unless otherwise
stated. Coupling constants (J) are quoted in Hz.
The minor (5-carboxylate) isomer 9b was identified from the
1H NMR spectrum of the mixture; δH 8.25 (1H, s), 6.40 (1H, s),
3.85 (3H, s) and 1.38 (9H, s).
Preparation of azides. General method5
The appropriate amine (10 mmol) was dissolved in hydrochloric
acid (5 , 15 cm3) and cooled to < 0 ЊC. A solution of sodium
nitrite (0.76 g, 11 mmol) dissolved in water (5 cm3, cooled to
< 0 ЊC) was added and the mixture was stirred for 5–10 min. A
solution of sodium azide (0.98 g, 15 mmol) in water (5 cm3) was
cautiously added and the mixture was left to stir (at < 0 ЊC) for
a further 30 min; a precipitate usually formed in the reaction
vessel. The mixture was extracted with dichloromethane (3 × 25
cm3) and the organic extracts were dried over magnesium sul-
fate. The dichloromethane was removed in vacuo to give the
azide as a solid which was pure enough for further use and
characterisation.
Methyl 1-(3-phenyl-1H-pyrazol-5-yl)-1H-1,2,3-triazole-4-
carboxylate 10
A solution of 5-azido-3-phenylpyrazole 6 (0.37 g, 2 mmol) and
methyl prop-2-ynoate 7 (0.351 g, 0.372 cm3, 4.2 mmol) in
acetonitrile (6 cm3) was heated to reflux under a nitrogen
atmosphere for 4 h. On cooling a white precipitate was
obtained. This was identified as methyl 1-(3-phenyl-1H-pyrazol-
5-yl)-1H-1,2,3-triazole-4-carboxylate 10 (0.24 g, 45%), mp 254–
255 ЊC (from ethanol) (Found: C, 57.2; H, 4.15; N, 25.0.
C13H11N5O2ؒ0.25H2O requires C, 57.05; H, 4.2; N, 25.6%);
δH ([2H6]DMSO) 13.85 (1H, br s), 9.22 (1H, s), 7.87–7.42 (5H,
m), 7.27 (1H, s) and 3.88 (3H, s); δC([2H6]DMSO) 160.35 (q),
145.39 (q), 144.37 (q), 138.97 (q), 129.09, 128.98, 128.12 (q),
126.64, 125.33, 94.68 and 51.94; m/z 269 (Mϩ, 46%), 240 (62),
238 (14), 210 (100), 198 (23), 183 (37) and 170 (17).
5-Azidopyrazole 4. From 5-aminopyrazole 1 (0.504 g, 46%),
mp 57–58 ЊC (lit.,5 60 ЊC); νmax/cmϪ1 2130.
5-Azido-3-tert-butylpyrazole 5. From 5-amino-3-tert-butyl-
pyrazole 2 (1.63 g, 99%), mp 94–95 ЊC (HRMS: Found Mϩ,
165.1003. C7H4N5 requires M, 165.1014); νmax/cmϪ1 2125; δH
12.54 (1H, br s), 5.84 (1H, s) and 1.34 (9 H, s); δC 156.87 (q),
146.26 (q), 92.16, 31.55 (q) and 29.70; m/z 165 (Mϩ, 51%), 137
(14), 108 (38), 94 (43), 81 (42) and 67 (100).
5-Azido-3-phenylpyrazole 6. From 5-amino-3-phenylpyrazole
3 (1.77 g, 96%), mp 147–148 ЊC (HRMS: Found Mϩ, 185.0703.
C9H7N5 requires M, 185.0701); νmax/cmϪ1 2120; δH ([2H6]ace-
tone) 7.79–7.73 (2H, m), 7.50–7.33 (3H, m) and 6.64 (1H, s);
δC([2H6]acetone) 147.65 (q), 144.15 (q), 128.11, 127.72, 124.35
and 92.13, one quaternary absent; m/z 185 (Mϩ, 48%), 159 (4),
157 (6), 129 (20), 128 (90), 102 (100) and 77 (43).
Dimethyl 1-(3-phenyl-1H-pyrazol-5-yl)-1H-1,2,3-triazole-4,5-
dicarboxylate 11
A solution of 5-azido-3-phenylpyrazole 6 (0.37 g, 2 mmol) was
dissolved in acetonitrile (5 cm3). Dimethyl acetylenedicarboxy-
late (0.284 g, 0.246 cm3, 2 mmol) was added and the mixture,
under a nitrogen atmosphere, was heated to reflux for 8 h.
On cooling a white precipitate formed which was identified
as dimethyl 1-(3-phenyl-1H-pyrazol-5-yl)-1H-1,2,3-triazole-4,5-
dicarboxylate 11 (0.200 g, 30%), mp 195–196 ЊC (from acetic
acid) (Found: C, 54.2; H, 4.1; N, 21.2. C15H13N5O4ؒ0.2H2O
requires C, 54.45; H, 4.05; N, 21.2%); δH ([2H6]DMSO) 7.89–
7.85 (2H, m), 7.56–7.43 (3H, m), 7.33 (1H, s), 3.96 (3H, s) and
3.91 (3H, s); δC([2H6]DMSO) 159.55 (q), 159.39 (q), 144.92 (q),
2-Azidoimidazole. From 2-aminoimidazole sulfate (0.35 g,
64%), mp 138 ЊC (decomp.) [lit.,19 140 ЊC (decomp.)]; νmax/cmϪ1
2122.
1802
J. Chem. Soc., Perkin Trans. 1, 1997

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144.82 (q), 137.10 (q), 131.37 (q), 129.33, 128.09, 125.64, 95.74,
54.13 and 52.78 (1 quarternary absent); m/z 327 (Mϩ, 21%), 268
(29), 267 (100), 224 (12), 209 (20) and 185 (15).
1,2,3-triazole-4-carboxylate 9a (0.238 g, 98%), identical in all
respects with that prepared by cycloaddition.
Pyrolysis of methyl 1-(1H-pyrazol-5-yl)-1H-1,2,3-triazole-4-
carboxylates
Reactions of 5-azido-3-tert-butylpyrazole 5 with other dienophiles
5-Azido-3-tert-butylpyrazole 5 (0.33 g, 2 mmol) was dissolved
in toluene (5–10 cm3) and reacted with the following dieno-
philes under various conditions.
With ethyl phenylprop-2-ynoate (0.348 g, 2 mmol) the
mixture was heated to reflux for 4 h. Removal of solvent in
vacuo yielded only decomposition products.
With phenylacetylene (0.202 g, 2 mmol), the mixture was
heated to reflux for 5 h. Reduced pressure evaporation of sol-
vent only yielded starting material and decomposition products.
With phenyl vinyl sulfoxide (0.450 g, 3 mmol) the mixture was
heated to reflux for 5 h. Removal of solvent in vacuo yielded
decomposition products.
With ethyl (trimethylsilyl)prop-2-ynoate (0.485 g, 2.5 mmol)
the mixture was heated to reflux for 12 h. Removal of solvent
gave an intractable mixture.
The triazoles were sublimed at 1 × 10Ϫ3 Torr into a horizontal
silica furnace tube (35 × 2.5 cm), which was maintained at a
temperature of 600 ЊC by an electrical heater. The quantity of
precursor, inlet temperature and pyrolysis time of the FVP
experiments are indicated in parentheses. The products con-
densed at the exit point of the furnace and were recovered from
the trap by scraping with a spatula. They were glassy in appear-
ance and could not be successfully purified by crystallisation.
The unsubstituted compound 8a (0.170 g, inlet 130 ЊC, 45
min) gave 5-methoxy-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one
16 (0.060 g, 42%), mp 203–205 ЊC (HRMS: Found Mϩ,
165.0538. C7H7N3O2 requires M, 165.0538); δH ([2H6]DMSO)
3
3
7.78 (1H, d, J 1.8), 5.98 (1H, d, J 1.8), 5.26 (1H, s) and 3.90
(3H, s); δC([2H6]DMSO) 161.19 (q), 157.33 (q), 142.16, 139.79
(q), 88.50, 75.10 and 56.51; m/z 165 (Mϩ, 100%), 164 (22), 134
(24), 122 (13), 107 (22) and 106 (11).
Reaction of 2-azidoimidazole 12 and methyl prop-2-ynoate 7
2-Azidoimidazole 12 (0.350 g, 2 mmol) was treated with methyl
prop-2-ynoate 7 (0.566 g, 0.60 cm3, 6.7 mmol) in toluene. The
mixture was heated to reflux for 3 h during which time a brown
precipitate formed which was found to be polymeric material.
Removal of solvent yielded decomposition products.
The 3-tert-butyl derivative 9a (0.71 g, inlet 140 ЊC, 3 h) gave
2-tert-butyl-5-methoxy-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-
one 17 (0.350 g, 50%), mp 207–209 ЊC (HRMS: Found Mϩ,
221.1155. C11H15N3O2 requires M, 221.1164); δH ([2H6]DMSO)
5.86 (1H, s), 5.20 (1H, s), 3.88 (3H, s) and 1.27 (9H, s);
δC([2H6]DMSO) 163.79 (q), 160.88 (q), 157.25 (q), 139.88 (q),
85.15, 75.02, 56.55, 32.22 (q) and 29.87; m/z 221 (Mϩ, 96%), 220
(40), 206 (100), 179 (40) and 174 (30).
The 3-phenyl derivative 10 (0.168 g, inlet 160 ЊC, 2 h) gave
5-methoxy-2-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one
18 (0.080 g, 53%), mp 167–169 ЊC (HRMS: Found Mϩ,
241.0850. C13H11N3O2 requires M, 241.0851); δH ([2H6]DMSO)
7.97–7.92 (2H, m), 7.51–7.38 (3H, m), 6.45 (1H, s), 5.31 (1H, s)
and 3.92 (3H, s); δC([2H6]DMSO) 160.80 (q), 157.20 (q), 152.72
(q), 140.41 (q), 132.67 (q), 128.63 (2C), 125.93, 85.45, 75.35 and
56.85; m/z 241 (Mϩ, 100), 240 (22), 227 (9), 213 (14), 212 (13),
210 (11), 198 (15), 173 (16) and 159 (16).
Ethyl 2-formyl-2-diazoacetate 138
Prepared by the literature method from N,N-dimethylchloro-
methaniminium chloride (4.18 g, 32.5 mmol) and ethyl diazo-
acetate (3.74 g, 3.44 cm3, 32.5 mmol) (added via syringe pump)
in dry chloroform (12 cm3) at Ϫ8 ЊC under a nitrogen atmo-
sphere, the product (1.10 g, 30%) was purified by Kugelrohr dis-
tillation, bp 81–82 ЊC/10 Torr (lit.,8 82–83 ЊC/10 Torr); δH 9.54
3
3
(1H, s), 4.22 (2H, q, J 7.1) and 1.22 (3H, t, J 7.1); δC 181.10,
160.83 (q), 61.56 and 13.86 (one quaternary absent).
Ethyl 1-phenyl-1H-1,2,3-triazole-4-carboxylate 198
Dimethyl
1-(3-phenyl-1H-pyrazol-5-yl)-1H-1,2,3-triazole-
Ethyl 2-formyl-2-diazoacetate 13 (0.426 g, 3 mmol) was dis-
solved in ethanol (3 cm3). A solution of aniline (0.27 g, 2.9
mmol) in ethanol (1.8 cm3) and acetic acid (0.6 cm3) was added
and the mixture was stirred at room temperature for 16 h. On
removal of solvent a solid was obtained, and crystallisation from
ethanol gave white needles of ethyl 1-phenyl-1H-1,2,3-triazole-
4-carboxylate 19 (0.450 g, 70%), mp 86–87 ЊC (lit.,8 88 ЊC).
4,5-dicarboxylate 11 (0.051 g, inlet 155 ЊC, 1 h 15 min) gave a
mixture which showed at least four spots by TLC, and so this
pyrolysis was not pursued further.
Pyrolysis of ethyl 1-phenyl-1H-1,2,3-triazole-4-carboxylate 19
FVP of the ethyl ester (0.083 g) at 600 ЊC (1 × 10Ϫ3 Torr, inlet
temperature 130 ЊC) for 1 h gave a product which was identified
as quinoline-2,4-diol as its 4-keto tautomer 21, by comparison
with an authentic sample whose δH values are quoted in square
brackets after the corresponding pyrolysate values; δH ([2H6]-
Ethyl 1-(3-tert-butyl-1H-pyrazol-5-yl)-1H-1,2,3-triazole-4-
carboxylate 14, and its conversion to the methyl ester 9a
5-Amino-3-tert-butylpyrazole 2 (0.278 g, 2 mmol) was dis-
solved in ethanol (1.2 cm3) and acetic acid (0.4 cm3). A solution
of ethyl 2-formyl-2-diazoacetate 13 (0.284 g, 2 mmol) in etha-
nol (2 cm3) was added and the mixture was stirred for 16 h. On
removal of solvent, a yellow solid was obtained, which was
identified as ethyl 1-(3-tert-butyl-1H-pyrazol-5-yl)-1H-1,2,3-
triazole-4-carboxylate 14 (0.427 g, 81%), mp 155–156 ЊC (from
cyclohexane–ethyl acetate) (Found: C, 54.7; H, 6.35; N, 25.95.
C12H17N5O2ؒ0.1H2O requires C, 54.5; H, 6.5; N, 26.4%); δH
3
DMSO) 11.22 (1H, s) [11.24 (1H, s)], 7.78 (1H, d, J 7.9) [7.78
3
(1H, d, J 8.0)], 7.53–7.44 (1H, m) [7.53–7.45 (1H, m)], 7.28–
7.09 (2H, m) [7.29–7.09 (2H, m)] and 5.75 (1H, s) [5.76 (1H, s)];
δC([2H6]DMSO) 163.72 (q), 162.58 (q), 139.27 (q), 130.95,
122.76, 121.19, 115.26, 115.22 (q) and 98.32.
13C Isotopic labelling experiment
Dimethyl[13C]formamide (0.250 g) was reacted with oxalyl
chloride (0.428 cm3) to give N,N-dimethylchloro[13C]-
methaniminium chloride (0.436 g) as previously described.20
The salt was then reacted with ethyl diazoacetate (0.710 cm3)
under the conditions described above to give ethyl 2-
[13C]formyl-2-diazoacetate 13* (0.116 g). Ethyl 2-[13C]formyl-2-
diazoacetate (0.071 g) was then reacted with 5-amino-3-tert-
butylpyrazole 2 (0.069 g) to give, after ester exchange (Na–
MeOH), methyl 1-(3-tert-butyl-1H-pyrazol-5-yl)-1H-[5-13C]-
1,2,3-triazole-4-carboxylate 9a * (0.046 g, 41%); δC([2H6]-
acetone) 124.24 {δC([2H]chloroform) 126.59, isotopically
enhanced}. Pyrolysis of 9a * (0.028 g, 140 ЊC, 1 h) at 600 ЊC
returned 2-tert-butyl-5-methoxy-4,7-dihydro[5-13C]pyrazolo-
[1,5-a]pyrimidin-7-one 17*; δC([2H6]DMSO) 160.92 (q) (iso-
3
3
10.12 (1H, s), 6.63 (1H, s), 4.55 (2H, q, J 7.1), 1.47 (3H, t, J
7.1) and 1.41 (9H, s); δC 162.32 (q), 155.64 (q), 145.75 (q),
139.61 (q), 126.61, 92.78, 61.95, 31.28 (q), 29.79 and 14.07; m/z
263 (Mϩ, 44%), 220 (84), 190 (100), 174 (59), 164 (50), 163 (86)
and 148 (79).
Ethyl 1-(3-tert-butyl-1H-pyrazol-5-yl)-1H-1,2,3-triazole-4-
carboxylate (0.263 g, 1 mmol) was treated with a solution of
sodium methoxide [from sodium (0.05 g)] in methanol (5 cm3).
The mixture was stirred at room temperature for 3 h, poured
into water and neutralised with dilute hydrochloric acid. The
solution was extracted with dichloromethane (3 × 10 cm3)
and the extracts were dried over magnesium sulfate. Removal
of solvent gave methyl 1-(3-tert-butyl-1H-pyrazol-5-yl)-1H-
J. Chem. Soc., Perkin Trans. 1, 1997
1803

View Article Online
topically enriched). An unidentified impurity peak was
Themethylthio derivative32[0.087g, inlet 180 ЊC, 2h, 1 × 10Ϫ4
recorded at δ 165.01.
Torr (mercury diffusion pump)] gave 2-tert-butyl-5-methylthio-
4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one 37 (0.033 g, 53%), mp
319–320 ЊC (HRMS:Found Mϩ, 237.0940. C11H15N3OSrequires
M, 237.0936); δH ([2H6]DMSO) 5.92 (1H, s), 5.55 (1H, s), 2.57
(3H, s) and 1.29 (9H, s); δC([2H6]DMSO) 164.25 (q), 154.82 (q),
152.70 (q), 141.76 (q), 91.22, 84.76, 32.28 (q), 29.90 and 13.94;
m/z 237 (Mϩ, 100%), 222 (23), 190 (60) and 174 (13).
2,2-Dimethyl-1,3-dioxane-4,6-diones 30, 31 and 38
The appropriate amino compound (5 mmol) and 5-
methoxymethylene-2,2-dimethyl-1,3-dioxane-4,6-dione21
33
(0.93 g, 5 mmol) were dissolved in acetonitrile (25 cm3) and the
solution was stirred at room temperature for 15 min. The pre-
cipitate which formed was filtered to give the product.
The 3-aminotriazole derivative 38 (0.93 g, inlet 140 ЊC, 5 h)
gave at 700 ЊC an inseparable mixture of 4,7-dihydro-1,2,4-
triazolo[1,5-a]pyrimidin-7-one 39 (major product, see Discus-
sion section) and 5,8-dihydro-1,2,4-triazolo[4,3-a]pyrimidin-5-
one 40 (0.400 g, 76%) (the parameters of the minor product 40
are quoted in parentheses); δH ([2H6]DMSO) 8.23 (1H, s) [9.05
5-(N-Pyrazol-3-ylaminomethylene)-2,2-dimethyl-1,3-dioxane-
4,6-dione 30. From 3-aminopyrazole (1.18 g, 95%), mp 195–
196 ЊC (from ethanol) (Found: C, 50.2; H, 4.6; N, 17.6.
C10H11N3O4 requires C, 50.6; H, 4.65; N, 17.7%); δH 11.30 (1H,
br s), 8.75 (1H, s), 7.56 (1H, d, J 2.5), 6.23 (1H, d, J 2.5) and
1.74 (6H, s); δC 165.11 (q), 163.56 (q), 153.31, 148.11 (q),
130.33, 104.99 (q), 94.43, 86.91 (q) and 26.86; m/z 237 (Mϩ,
12%), 179 (29), 161 (100) and 107 (22).
5-[N-(5-Methylpyrazol-3-yl)aminomethylene]-2,2-dimethyl-
1,3-dioxane-4,6-dione 31. From 3-amino-5-methylpyrazole
(1.15 g, 92%), mp 188–189 ЊC (from ethanol) (Found: C, 52.7;
H, 5.4; N, 16.8. C11H13N3O4 requires C, 52.6; H, 5.2; N, 16.75%);
δH 11.28 (1H, br s), 8.68 (1H, br s), 5.95 (1H, s), 2.31 (3H, s) and
1.73 (6H, s); δC 165.04 (q), 163.67 (q), 153.14, 148.29 (q), 141.20
(q), 104.89 (q), 93.49, 86.62 (q), 26.83 and 11.02; m/z 251 (Mϩ,
15%), 193 (31), 175 (100), 149 (4) and 121 (12).
3
3
3
3
(1H, s)], 7.98 (1H, both isomers, d, J 7.4) and 5.94 (1H, d, J
7.4) [5.77 (1H, d, J 7.4)]; δC([2H6]DMSO) 156.51 (q) [156.05
3
(q)], 151.93 (148.20), 150.79 (q) [149.36 (q)], 140.60 (133.23)
and 99.27 (96.92). When small-scale pyrolyses (0.050 g) were
carried out at different furnace temperatures (400–700 ЊC) (inlet
140 ЊC, 1 × 10Ϫ3 Torr), varying proportions of the two products
were obtained; ratios were determined from the integral values
obtained for the peaks at δH 5.94 and 5.77. The relative propor-
tions of the two isomers 40:39 are as follows: 400 ЊC, 64:36;
500 ЊC, 42:58; 600 ЊC, 36:64; 700 ЊC, 31:69.
5-[N-(1,2,4-Triazol-3-yl)aminomethylene]-2,2-dimethyl-1,3-
dioxane-4,6-dione 38. From 3-amino-1,2,4-triazole (1.04 g,
86%), mp 208–209 ЊC (decomp., from ethanol) (Found: C, 45.3;
H, 4.35; N, 23.4. C9H10N4O4 requires C, 45.4; H, 4.2; N, 23.5%);
δH ([2H6]DMSO) 14.11 (1H, br s), 11.20 (1H, br s), 8.75 (1H, s),
8.55 (1H, s) and 1.68 (6H, s); δC([2H6]DMSO) 163.88 (q), 162.32
(q), 156.28 (q), 152.37, 144.74, 104.67 (q), 87.91 (q) and 26.45;
m/z 238 (Mϩ, 24%), 181 (18), 180 (93), 163 (13), 136 (35), 134
(11), 108 (100) and 81 (15).
Acknowledgements
We are grateful to Kodak Ltd. and the EPSRC for a CASE
award to R. W. M. We acknowledge the assistance of Mr M. C.
Evans in assigning the isomeric triazolopyrimidinones.
References
1 Preliminary communication: D. Clarke, R. W. Mares and
H. McNab, J. Chem. Soc., Chem. Commun., 1993, 1026.
2 T. L. Gilchrist, G. E. Gymer and C. W. Rees, J. Chem. Soc., Perkin
Trans. 1, 1975, 1.
3 G. Mitchell and C. W. Rees, J. Chem. Soc., Perkin Trans. 1, 1987, 413.
4 B. E. Fulloon and C. Wentrup, J. Org. Chem., 1996, 61, 1363.
5 E. Alcalde, J. de Mendoza and J. Elguero, J. Heterocycl. Chem.,
1974, 11, 921.
6 A. Padwa, in 1,3-Dipolar Cycloaddition Chemistry, ed. A. Padwa,
Wiley, New York, 1984, vol. 1, p. 621.
7 I. Fleming, Frontier Orbitals and Organic Chemical Reactions, Wiley,
Chichester, 1976, p. 156.
8 F. M. Stojanovic and Z. Arnold, Collect. Czech. Chem. Commun.,
1967, 32, 2155.
9 J. Elguero, R. Jacquier and S. Mignonac-Mondon, J. Heterocycl.
Chem., 1973, 10, 411.
10 N. Al-Awadi, J. Ballam, P. R. Hemblade and R. Taylor, J. Chem.
Soc., Perkin Trans. 2, 1982, 1175.
11 For example, W. D. Crow and H. McNab, Aust. J. Chem., 1979, 32, 89.
12 C. Wentrup, Adv. Heterocycl. Chem., 1981, 28, 232.
13 For example, C. O. Kappe, G. Kollenz, R. Leung-Toung and
C. Wentrup, J. Chem. Soc., Chem. Commun., 1992, 487.
14 P. E. Hansen, Prog. Nucl. Magn. Reson. Spectrosc., 1981, 14, 175.
15 J. L. G. Ruano, C. Pedregal and J. H. Rodriguez, Heterocycles, 1991,
32, 2151.
16 R. Faure, E. J. Vincent, R. M. Claramunt and J. Elguero, Org.
Magn. Reson., 1978, 9, 508.
17 G. Auzzi, F. Bruni, L. Cecchi, A. Costanzo, L. P. Vettori, R. Pirisino,
M. Corrias, G. Ignesti, G. Banchelli and L. Raimondi, J. Med.
Chem., 1983, 26, 1706.
18 J. Reiter, L. Pongó and P. Dvortsák, Tetrahedron, 1987, 43, 2497.
19 M. Rull and J. Vilarrasa, J. Heterocycl. Chem., 1977, 14, 33.
20 T. Fujisawa and T. Sato, Org. Synth., 1988, 66, 121.
21 G. A. Bihlmayer, G. Derflinger, J. Derkosch and O. E. Polansky,
Monatsh. Chem., 1967, 98, 564.
5-{Methylthio[N-(5-tert-butylpyrazol-3-yl)amino]methylene}-
2,2-dimethyl-1,3-dioxane-4,6-dione 32
5-[Bis(methylthio)methylene]-2,2-dimethyl-1,3-dioxane-4,6-
dione22 34 (0.496 g, 2 mmol) was reacted with 5-amino-3-tert-
butylpyrazole 2 (0.278 g, 2 mmol) in acetonitrile (4 cm3). The
mixture was first heated to reflux for 2 h and then was stirred at
room temperature for a further 16 h. On removal of solvent in
vacuo an oil was obtained; this was purified by chromatography
(silica, 50:50 ethyl acetate–hexane) to give 5-{methylthio[N-
(5-tert-butylpyrazol-3-yl) amino]methylene}-2,2-dimethyl-1,3-
dioxane-4,6-dione 32 (0.234 g, 35%), mp 134–135 ЊC (HRMS:
Found M ϩ 1 [FAB], 340.1331. C15H22N3O4S requires M ϩ 1,
340.1331); δH 12.76 (1H, br s), 6.10 (1H, s), 2.34 (3H, s), 1.72
(6H, s) and 1.32 (9H, s); δC 177.88 (q), 163.79 (q), 155.01 (q),
145.65 (q), 103.00 (q), 96.99, 86.13 (q), 31.13 (q), 29.83, 26.19
and 18.65; m/z (electron impact) 281 (Mϩ Ϫ 58, 33%), 263 (60),
248 (48), 237 (67), 222 (38), 221 (33) and 190 (100).
Pyrolysis reactions of 2,2-dimethyl-1,3-dioxane-4,6-diones
The compounds were pyrolysed under FVP conditions at a tem-
perature of 600 ЊC and a pressure of 0.001 Torr. The products
were formed at the exit of the furnace tube and were scraped
out of the trap with a spatula.
The 3-aminopyrazole derivative 30 (0.500 g, inlet 120 ЊC, 2 h)
gave 4,7-dihydropyrazolo[1,5-a]pyrimidin-7-one 35 (0.136 g,
48%), mp 238–240 ЊC (lit.,23 239–240 ЊC); δH ([2H6]DMSO) 7.88
(1H, d, 3J 7.3), 7.87 (1 H, d, 3J 2.0), 6.19 (1H, d, 3J 2.0) and 5.69
3
(1H, d, J 7.3); δC([2H6]DMSO) 156.65 (q), 142.58, 141.85 (q),
22 X. Huang and B.-C. Chen., Synthesis, 1987, 480.
23 C. K. Chu, J. J. Suh, M. Mesbah and S. J. Cutler, J. Heterocycl.
Chem., 1986, 23, 349.
139.53, 95.15 and 88.97.
The 3-amino-5-methylpyrazole derivative 31 (0.507 g, inlet
190 ЊC, 105 min) gave 2-methyl-4,7-dihydropyrazolo[1,5-a]-
pyrimidin-7-one 36 (0.156 g, 52%), mp 274–277 ЊC (lit.,17
275–280 ЊC); δH ([2H6]DMSO) 7.79 (1H, d, J 7.3), 6.01 (1H, s),
Paper 7/00421D
Received 17th January 1997
Accepted 7th March 1997
3
5.62 (1H, d, 3J 7.3) and 2.28 (3H, s); δC([2H6]DMSO) 156.29 (q),
151.74 (q), 142.20 (q), 138.89, 95.25, 88.64 and 13.96.
1804
J. Chem. Soc., Perkin Trans. 1, 1997